Jumping Genes Challenge Assumptions About Genetic Diseases Such As Cancer

Jumping genes do their jumping while the embryo is growing and not when sperm and eggs are developing, according to a new study by US
scientists which challenges current assumptions about the timing of when mobile DNA inserts itself into the human genome. The finding could have
important implications for genetic research into rare diseases that are thought to be caused by jumping genes.

The study was conducted by senior author Dr Haig H. Kazazian Jr, Seymour Gray Professor of Molecular Medicine in Genetics at the University of
Pennsylvania School of Medicine in Philadelphia, and colleagues, and is published this month in the journal Genes and
Development.

Transposons, or "jumping genes", are DNA sequences that jump to different parts of the genome within a cell.

Transposons cause disease but we don't know the extent to which the diseases they cause, such as hemophilia and Duchenne muscular dystrophy, are
passed onto offspring. They also play a role in the development of cancer.

Kazazian Jr and colleagues found that transposons insertion can occur after fertilization, when the embryo is developing, which is after the point at
which genetic changes can be inherited: ie they happen once the individual is formed from the egg and sperm of the bioligical parents.

Based on their findings, the researchers propose that many of the insertions occur in the early embryo, while it comprises just 4 or 8 cells.

This is a dramatic challenge to current assumptions about mobile DNA, which until now scientists assumed could only be inserted in the genome prior
to fertlization, in egg and sperm of the parents.

For the study, Kazazian Jr and colleagues looked at the L1 family of retrotransposons, the most common type of retrotransposon in the human
genome.

A retrotransposon is a type of jumping gene that moves in a distinct way: its DNA sequence is copied to RNA as with other genes, but instead of being
used directly to code a protein, it is then copied back into DNA under the control of its own reverse transcriptase enzyme. This new DNA sequence is
then put back into the genome.

The process is similar to the way that HIV and other retroviruses behave, leading scientists to suggest that retroviruses came from
retrotransposons.

About 17 per cent of the human genome is made up of the L1 family of retrotransposons, so they are no small matter and they have an impact that is
even larger than this. For example, when they "jump" they take parts of nearby DNA sequences with them, causing new genes to be created where they
eventually "land".

Eventually, as one can imagine, the more that retrotransposons jump around the genome, the longer it gets and the more its content gets shuffled. As
well as this, an otherwise unremarkable jump of L1 can have a significant impact such as lowering the ability of nearby genes to express
themselves.

L1 insertions come about in two ways: one is where the L1 RNA is carried over from the parent through fertilization and then gets inserted in the
embryo's genome. The other and more frequent way, is when the L1 itself arises in the embryonic genome.

Using mice and rats bred to have elements of human L1, the researchers showed there was lots of L1 RNA in egg, sperm and embryos. But they also
showed that integration into the genome occured primarily at the embryo development stage and not within egg and sperm cells and were therefore not
inheritable.

Kazazian Jr and colleagues also showed that L1 RNA transcribed in egg and sperm cells carry over through fertilization and insert during embryo
development, which is a curious example of RNA being heriditary independently of the DNA that encodes it. This creates what the authors called
"somatic mosaicism" with some cells having the insertion and others not, leading to cell populations with different genotypes developing within the
same organism.

This mosaicism could suggest that L1 plays an important role in the development of cancer and other diseases, for instance if the insertion happens
near a cancer gene, it could trigger cancer growth.

Please note: If no author information is provided, the source is cited instead.

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